Blood PhysiologyAllison Gourley and Susan Rutherford

Define Haematopoesis

• Production of mature blood cells• Red, white, platelets

Where does haematopoiesis occur? [3]• Yolk sac (trimester one)• Liver and spleen (trimester two)• Red marrow (trimester three

onwards)

Where does haematopoiesis occur? [3]• Yolk sac (trimester one)• Liver and spleen (trimester two)• Red marrow (trimester three

onwards)Where is red marrow found? [2]

Flat bones: pelvis, sternum, ribs, scapula, craniumEpiphyseal ends of long bones: femur, humerus

Myeloid stem cell (GEMM) Lymphoid stem cell

Multipotent hematopoietic stem cell

What are the two different types of stem cells that arise from

Myeloid stem cell

B-lymphoblast T-lymphoblast

B-cells T-cells

Lymphoid Stem Cell

Plasma cells

Multipotent hematopoietic stem cell

14 days

What types of cells are produced from the myeloid cell line?

RBC, Platelets, Neutrophils, Macrophages, Eosinophils, Mast cells

What controls haematopoiesis? [2]

• Local cell-to-cell contacts• Growth factors (Now, name the 2 growth factors involved) • Paracrine (G-CSF) or endocrine (EPO)• Control proliferation, differentiation, maturation

EPO speeds erythropoiesis by what two mechanisms?

• Increases rate of mitoses• Decreases maturation time

What four things are required? [4]

• EPO, iron, folic acid, vitB12

Steps of erythropoiesis?

Name some of the changes that occur to the cell during erythropoiesis:

•Decrease in cell size•Haemoglobin production•Loss of organelles•Acquires an eosinophilic cytoplasm•Extrusion of nucleus•Acquisition of a biconcave disc

Four reasons for an erythrocyte being a biconcave disc? [4]

• Increase surface area•Minimise distance (for diffusion)

• Increase flexibility•Minimal tension with cell swelling

What is polycythaemia?

• Too many erythrocytes

•Opposite: anaemia

What is the pathogenesis of sickle cell anaemia?

• Autosomal recessive• Point mutation of HbS• leads to extensive membrane

damage, producing an irreversibly sickled cell resulting in haemolysis

Where in the body is iron found?

• Haemoglobin• Circulating, bound to transferrin• Hepatocytes• Macrophages• Intracellular stores – ferritin and

haemosiderin

What marker would you measure to investigate a patient’s iron stores?

• Ferritin:Circulating levels reflect iron stores

What are 3 causes of iron deficiency?

1. Increased demand2. Inadequate absorption3. Blood loss

Describe the stages leading to iron deficiency anaemia

Net loss of ironExhaustion of iron stores

Decreased serum iron

Compensatory increase in iron binding capacity

Saturation of transferrin <15% leading to reduced iron delivery to bone marrow

Iron deficiency anaemia

Initial Compensationand effect Continues End result

Describe the passage of vitamin B12 through the body

1. Vitamin B12 ingested2. Is bound R protein in

salivary fluid3. Binds to intrinsic

factor in the duodenum

4. Absorbed in terminal ileum

What is the only indispensible function of the stomach?

Secretion of intrinsic factor

What is pernicious anaemia?

Autoimmune destruction of gastric parietal cells

leading to lack of intrinsic factor and hence, B12 deficiency

What is the most common cause of vitamin B12 deficiency?

• Malabsorption

• NB. Rarely due to insufficient intake

What are some other causes of B12 deficiency?

• Gastric causes e.g. gastrectomy• Intestinal causes e.g. malabsorption,

ileal resection, Crohn’s disease (remember effect on terminal ileum), HIV, radiotherapy

• Some drugs e.g. anticonvulsants

Give 4 causes of folic acid deficiency

1. Insufficient intake2. Malabsorption3. Drugs e.g alcohol, anticonvulsants4. Increased demand (leading to higher

turnover)

What are the body’s physiological responses to anaemia? (4)

• Decreased affinity of Hb for oxygen• Redistribute blood flow

(withdraw supply to skin and kidneys, increase plasma volume from interstitial fluid)

• Increase reticulocyte count• Increase cardiac output (only if severe)

What is the name for having too many WBCs? Why might this happen?

• Leukocytosis

• Increased production in marrow• E.g. infection, paraneoplastic syndrome, CML

• Increased release from marrow stores • E.g. infection, hypoxia

• Decreased margination• E.g. exercise, catecholamines

• Decreased extravasation into tissues• E.g. glucocorticoids

What is the name for having too few WBCs? Why might this happen?

• Leukopaenia

• Suppression of haematopoeitic stem cells• Suppression of committed granulocytic

precursors• Ineffective haematopoeisis• Increased peripheral utilisation

Types of anaemia and examples of their causes

Normocytic, normochromic

Acute blood lossAnaemia of chronic diseaseHaemolytic

anaemia

Microcytic, hypochromic

Iron deficiency

Thalassaemia

Macrocytic, normochromic

Vitamin B12 deficiencyFolate deficiency

Pernicious anaemia(accounts for 80% of this type)